RESUMO
The global surge in pharmaceutical consumption, driven by increasing population and the demand for animal proteins, leads to the discharge of diverse pollutants, including antibiotic residues, into water bodies. Sulfonamides, being water-soluble compounds, can readily enter surface run-off, posing potential risks to non-target species despite their low environmental concentrations. Latin America has implemented intensive production systems highly dependent on antimicrobials for productivity and animal health, yet there is a paucity of information regarding their concentration in the region. The objective of this study was to evaluate the presence of sulfonamides in water and sediment samples and assess their potential ecological risks through an environmental risk assessment. The Río de la Plata basin collects the waters of the Paraguay, Paraná, and Uruguay rivers, together with their tributaries and various wetlands, passing through the provinces in Argentina known for their significant animal husbandry production. Two sampling campaigns were carried out for sediment, while only one campaign was conducted for surface waters. The samples were analyzed by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS). None of the examined sulfonamide antibiotics were detected in the sediment samples from both sampling campaigns. In contrast, sulfadiazine (95 %), sulfamethoxazole (91 %), and sulfathiazole (73 %) were detected in the water samples. Sulfadiazine was found in the concentration range of 8 to 128 ng/L, while sulfamethoxazole and sulfathiazole were observed at concentrations ranging from 3.0 to 32.5 ng/L and 2.9 to 8.1 ng/L, respectively. Based on the environmental risk assessment conducted using the sulfonamide concentrations, most samples indicated a medium risk for aquatic biota, with only one sample surpassing the high-risk threshold. This study represents the first report presenting data on the presence of sulfonamide antibiotics in the aquatic environment of Argentina.
Assuntos
Monitoramento Ambiental , Sulfonamidas , Poluentes Químicos da Água , Argentina , Medição de Risco , Poluentes Químicos da Água/análise , Sulfonamidas/análise , Antibacterianos/análise , Rios/química , Sedimentos Geológicos/química , Espectrometria de Massas em TandemRESUMO
Antibiotics from sulfonamide, fluoroquinolone, and diaminopyrimidine classes are widely used in human and veterinary medicine, and their combined occurrence in the aquatic environment is increasing around the world. In parallel, the understanding of how mixtures of these compounds affect non-target species from tropical freshwaters is scarce. Thus, this work aimed to study the long-term reproductive, recovery, and swimming effects of mixtures of 12 antibiotics from three different classes (up to 10 µg L-1 ) added to freshwater (FWM) and synthetic wastewater (SWM) matrices on freshwater worm Allonais inaequalis. Results revealed that at the reproduction level, the exposure to antibiotics in the SWM matrix does not cause a significant toxic effect on species after 10 days. On the other hand, exposures to initial dose mixtures (10 µg L-1 each) in FWM caused a significant reduction of offspring by 19.2%. In addition, recovery bioassays (10 days in an antibiotic-free environment) suggested that A. inaequalis has reduced offspring production due to previous exposure to antibiotic mixtures in both matrices. Furthermore, despite slight variation in swimming speed over treatments, no significant differences were pointed out. Regarding antibiotics in the water matrices after 10-day exposures, the highest concentrations were up to 2.7, 7.8, and 4.2 µg L-1 for antibiotics from sulfonamide, fluoroquinolone, and diaminopyrimidine classes, respectively. These findings suggest that a species positioned between primary producers and secondary consumers may experience late reproductive damage even in an antibiotic-free zone, after previous 10-day exposure to antibiotic mixtures. PRACTITIONER POINTS: A mixture of sulfonamide, fluoroquinolone, and diaminopyrimidine antibiotics in freshwater affects the offspring production of A. inaequalis after 10 days. After the 10-day antibiotic exposure, the reproduction of A. inaequalis remains affected in an antibiotic-free environment over the recovery period. The swimming speed of the worms does not change after 10 days of exposure to the antibiotic mixture. The concentration of dissolved solids can limit the natural degradation of sulfonamide, fluoroquinolone, and diaminopyrimidine antibiotics in the aquatic environment.
Assuntos
Antibacterianos , Poluentes Químicos da Água , Humanos , Águas Residuárias , Natação , Fluoroquinolonas/análise , Fluoroquinolonas/toxicidade , Sulfanilamida , Sulfonamidas , Água Doce , Reprodução , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análiseRESUMO
Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007R) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 µg/mL and 128 µg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 µg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Humanos , Simulação de Acoplamento Molecular , Cromonas/farmacologia , Escherichia coli , Bases de Schiff/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Sulfanilamida , Ampicilina/farmacologia , Sulfonamidas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Microbial contamination remains a significant economic challenge in the food industry, emphasizing the need for innovative antimicrobial solutions. In this study, we synthesized N-sulfonyl-1,2,3,4-tetrahydroisoquinolines (NSTHIQ) derivatives using an environmentally friendly Preyssler heteropolyacid catalyst, obtaining moderate to high yields (35-91 %) under mild conditions. Two derivatives (5 and 6) exhibited significant antifungal properties against various fungal species, including Aspergillus spp, Penicillium spp, and Botrytis cinerea. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis revealed the absence of hepatic toxicity in all compounds, making derivatives 2, 3, 4, and 5 potential candidates for further development. However, derivatives 6 and 7 exhibited immunotoxicity. In support of our experimental findings, reactivity indices were computed using Density Functional Theory principles, deriving valuable insights into the chemical properties of these derivatives. This study underscores the potential of NSTHIQ compounds as potent antifungal agents, coupled with the importance of employing environmentally friendly catalysts in drug discovery.
Assuntos
Anti-Infecciosos , Tetra-Hidroisoquinolinas , Testes de Sensibilidade Microbiana , Anti-Infecciosos/química , Antifúngicos/farmacologia , Antifúngicos/química , Aspergillus , Tetra-Hidroisoquinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
This work reports the development and application of a highly selective core@shell-based quantum dot-molecularly imprinted polymer (QD@MIP) sensor for the detection of sulfadiazine (SDZ)-an antibiotic which belongs to the sulfonamide family. The synthesis of the smart material or MIP (molecularly imprinted polymer) was carried out by a precipitation method directly on the quantum dot surface, which played the role of a fluorescent probe in the optical sensor. The synthesized polymer was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Fluorescence experiments were performed in order to evaluate the effects of pH, interaction time of the QD@MIP with the analyte and SDZ concentration in different matrices. Under optimized conditions, a linear concentration range of 10.0-60.0 ppm and a limit of detection of 3.33 ppm were obtained. The repeatability and reproducibility of the proposed QD@MIP were evaluated in terms of the RSD, where RSD values of less than 5% were obtained in both tests. Selectivity studies were carried out in the presence of four possible interfering substances with quenching properties, and the signals obtained for these interferents confirmed the excellent selectivity of the proposed sensor; the imprinting factor value obtained for SDZ was 1.64. Finally, the proposed sensor was applied in real animal-based food samples using a spiked concentration of SDZ, where the recovery values obtained were above 90% (experiments were performed in triplicate).
Assuntos
Compostos de Cádmio , Impressão Molecular , Pontos Quânticos , Animais , Antibacterianos , Polímeros Molecularmente Impressos , Pontos Quânticos/química , Compostos de Cádmio/química , Reprodutibilidade dos Testes , Impressão Molecular/métodos , Telúrio/química , Sulfanilamida , Sulfadiazina , Limite de DetecçãoRESUMO
Chagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi, transmitted by the barber insect. Currently, there are approximately 7 million infected people in the world, and it is estimated that 70 million people could contract this disease. The anacardic acid (AA) showed effectiveness in in silico and in vitro tests. The antichagasic potential of five sulfonamide molecules, derived from anacardic acid, was evaluated from a molecular approach based on the density functional theory (DFT), molecular dynamics (MD), and molecular docking (docking) calculations. Methyl 2-methoxy-6- (8- (methylsulfonamide) octyl) benzoate (SA1); 2-methoxy-6- (8- (phenylsulfonamide) octyl) benzoate (SA2); methyl 2-methoxy-6- (8- (2methylphenyl sulfonamide) octyl) benzoate (SA3); methyl 2-methoxy-6- (8-(methylphenylsulfonamide)octyl)benzoate (SA4); methyl2-(8-(2,5-dimethylphenylsulfonamide)octyl)-6-methoxybenzoate (SA5) were the investigated molecules. The DFT calculations were performed using the B3LYP/6-311+G (d, p) level of theory. The global and local reactivity data showed that SA1 shows the highest molecular reactivity, while SA2 is the most stable derivative. In addition, the structures of investigated molecules were confirmed by the linear correlations higher than 0.98 displayed between the experimental and calculated spectroscopic data (IR and NMR). Molecular docking of the molecules showed a greater prominence for the SA1, SA2, and SA4 molecules in the results of distances of ligand-cruzain. In molecular dynamics, SA2 obtained better stability due to greater interactions with important amino acids of cruzain.
Assuntos
Ácidos Anacárdicos , Simulação de Dinâmica Molecular , Humanos , Simulação de Acoplamento Molecular , Teoria da Densidade Funcional , Ácidos Anacárdicos/farmacologia , Espectroscopia de Ressonância Magnética , SulfonamidasRESUMO
Malaria is a public health problem that causes thousands of deaths, primarily in children in African regions. Artemisinin-based combination therapies (ACTs) have helped to save thousands of lives; however, due to Plasmodium's resistance to available treatments, there is a need to search for new low-cost drugs that act through different mechanisms of action to contain this disease. This review shows that compounds with sulfonamide moiety, possibly, act as inhibitors of P. falciparum carbonic anhydrases, moreover, when linked to a variety of heterocycles potentiate the activities of these compounds and may be used in the design of new antimalarial drugs.
RESUMO
Sulfanilamide (SFL) is used to prevent infections in honeybees. However, many regulatory agencies prohibit or establish maximum levels of SFL residues in honey samples. Hence, we developed a low-cost and portable electrochemical method for SFL detection using a disposable device produced through 3D printing technology. In the proposed approach, the working electrode was printed using a conductive filament based on carbon black and polylactic acid and it was associated with square wave voltammetry (SWV). Under optimized SWV parameters, linear concentration ranges (1-10 µmol L-1 and 12.5-35.0 µmol L-1), a detection limit of 0.26 µmol L-1 (0.05 mg L-1), and suitable RSD values (2.4% for inter-electrode; n = 3) were achieved. The developed method was selective in relation to other antibiotics applied in honey samples, requiring only dilution in the electrolyte. The recovery values (85-120%) obtained by SWV were statistically similar (95% confidence level) to those obtained by HPLC, attesting to the accuracy of the analysis and the absence of matrix interference.
Assuntos
Mel , Fuligem , Animais , Fuligem/química , Sulfanilamida , Eletroquímica , Eletrodos , Técnicas Eletroquímicas , Carbono/químicaRESUMO
Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs.
Assuntos
Hipersensibilidade a Drogas , Humanos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Sulfonamidas/efeitos adversos , Antibacterianos/efeitos adversos , Sulfanilamida , Reações CruzadasRESUMO
A series of structural analogs of aryl sulfonamide hybrid compounds were synthesised and their cytotoxic activity was evaluated against three human breast cancer cell lines (MCF-7, MDA-MB-231 and Hs 578T). The compounds were designed through electronic, hydrophobic and steric modifications using the chemical structure of N-{4-[(2-hydroxy-3-methoxy-5-propylphenyl)sulfamoyl]phenyl}acetamide (referred to as compound 7) as a starting point to then assess a structure-activity relationship (SAR) study. From the data generated, we observed that compounds 9, 10 and 11 (which have modifications in the substituents of the aryl sulfonamide), efficiently reduced the cell viability of MCF-7 and MDA-MB-231 cell cultures. Based on initial data, we selected compounds 10 and 11 for further investigations into their antiproliferative and/or cytotoxic profile against MDA-MB-231 cells, and we noted that compound 10 was the most promising compound in the series. Compound 10 promoted morphological changes and altered the dynamics of cell cycle progression in MDA-MB-231 cells, inducing arrest in G1/S transition. Taken together, these results show that the dihydroeugenol-aryl-sulfonamide hybrid compound 10 (which has an electron withdrawing nitro group) displays promising antiproliferative activity against MDA-MB-231 cell lines.
Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Sulfonamidas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Relação Estrutura-Atividade , Antineoplásicos/química , Linhagem Celular , Linhagem Celular Tumoral , Apoptose , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Most neurodegenerative diseases are multifactorial, and the discovery of several molecular mechanisms related to their pathogenesis is constantly advancing. Dopamine and dopaminergic receptor subtypes are involved in the pathophysiology of several neurological disorders, such as schizophrenia, depression and drug addiction. For this reason, the dopaminergic system and dopamine receptor ligands play a key role in the treatment of such disorders. In this context, a novel series of conformationally restricted N-arylpiperazine derivatives (5a-f) with a good affinity for D2/D3 dopamine receptors is reported herein. Compounds were designed as interphenylene analogs of the drugs aripiprazole (2) and cariprazine (3), presenting a 1,3-benzodioxolyl subunit as a ligand of the secondary binding site of these receptors. The six new N-arylpiperazine compounds were synthesized in good yields by using classical methodologies, and binding and guanosine triphosphate (GTP)-shift studies were performed. Affinity values below 1 µM for both target receptors and distinct profiles of intrinsic efficacy were found. Docking studies revealed that Compounds 5a-f present a different binding mode with dopamine D2 and D3 receptors, mainly as a consequence of the conformational restriction imposed on the flexible spacer groups of 2 and 3.
Assuntos
Doenças Neurodegenerativas , Receptores de Dopamina D3 , Dopamina/metabolismo , Humanos , Ligantes , Doenças Neurodegenerativas/tratamento farmacológico , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismoRESUMO
Herein we describe results for the synthesis and synthetic application of 4-amino-3-(arylselenyl)benzenesulfonamides, and preliminary evaluation of antioxidant, anti-edematogenic and antinociceptive properties. This class of compounds was synthesized in good yields by a reaction of commercially available sulfanilamide and diorganyl diselenides in the presence of 10â mol% of I2 . Furthermore, the synthesized compound 4-amino-3-(phenylselenyl)benzenesulfonamide (3 a) was evaluated on complete Freund's adjuvant (CFA)-induced acute inflammatory pain. Dose- and time-response curves of antinociceptive effect of compound 3 a were performed using this experimental model. Also, the effect of compound 3 a was monitored in a hot-plate test to evaluate the acute non-inflammatory antinociception. The open-field test was performed to evaluate the locomotor and exploratory behaviors of mice. Oxidative stress markers, such as glutathione peroxidase activity; reactive species, non-protein thiols, and lipid peroxidation levels were performed to investigate the antioxidant action of compound 3 a. Our findings suggest that the antioxidant effect of compound 3 a may contribute to reducing the nociception and suppress the signaling pathways of inflammation on the local injury induced by CFA. Thus, compound 3 a reduced the paw edema as well as the hyperalgesic behavior in mice, being a promising therapeutic agent for the treatment of painful conditions.
Assuntos
Analgésicos Opioides/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Compostos Organometálicos/farmacologia , Dor/tratamento farmacológico , Compostos de Selênio/farmacologia , Sulfonamidas/farmacologia , Analgésicos Opioides/síntese química , Analgésicos Opioides/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antioxidantes , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Adjuvante de Freund , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Camundongos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Estresse Oxidativo/efeitos dos fármacos , Compostos de Selênio/química , Relação Estrutura-Atividade , Sulfonamidas/química , BenzenossulfonamidasRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world. 5- Fluorouracil (5-FU) is a conventional and most effective drug used in the clinic for the treatment of CRC. However, the clinical use of 5-FU is limited due to the acquired resistance and systemic toxicity, such as hepatotoxicity and gastrointestinal toxicity. OBJECTIVE: Recent advances in nanomedicine are being exploited to develop nanoparticle platforms to overcome resistance and therapeutic delivery of active molecules. Here, we developed 5-FU loaded sulfadiazine-poly(lactide-co-glycolide) nanoparticles (SUL-PLGA NPs) to be applied in the colorectal cancer model. METHODS: We assessed the in vivo efficacy of the SUL-PLGA NPs to enhance the antitumor effect of 5-FU. RESULTS: In vivo treatment with 5-FU-SUL-PLGA NPs significantly reduced tumor growth in a colon cancer xenograft model compared to free 5-FU and 5-FU loaded non-targeted NPs. Treatment with 5-FU-SUL-PLGA NPs also increased blood vessel diameters within tumors, which could act in conjunction to enhance antitumor efficacy. In addition, 5-FU-SUL-PLGA NPs significantly reduced liver mass and lung mass, which are the most common metastasis sites of CRC, and decreased liver hepatotoxicity compared to free 5-FU drug and 5-FU loaded non-targeted NPs. CONCLUSION: Our findings suggest that the use of 5-FU-SUL-PLGA NPs is a promising strategy to enhance 5-FU efficacy against CRC.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Neoplasias do Colo , Nanopartículas , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Polímeros , SulfonamidasRESUMO
Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.
Assuntos
Indutores da Angiogênese/farmacologia , Chalconas/farmacologia , Membrana Corioalantoide/irrigação sanguínea , Inflamação/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Indutores da Angiogênese/toxicidade , Animais , Chalconas/toxicidade , Embrião de Galinha , Inflamação/induzido quimicamente , Regulação para CimaRESUMO
Tetracyclines and sulfonamides are broad-spectrum antibacterial agents which have been used to treat bacterial infections for over half a century. The widespread use of tetracyclines and sulfonamides led to the emergence of resistance in a diverse group of bacteria. This resistance can be studied by searching for resistance genes present in the bacteria responsible for different resistance mechanisms. Salmonella is one of the leading bacteria causing foodborne diseases worldwide, and its resistance to tetracyclines and sulfonamides has been widely reported. The literature review searched the Virtual Health Library for articles with specific data in the studied samples: the resistance genes found, the primers used in PCR, and the thermocycler conditions. The results revealed that Salmonella presented high rates of resistance to tetracycline and sulfonamide, and the most frequent samples used to isolate Salmonella were poultry and pork. The tetracycline resistance genes most frequently detected from Salmonella spp. were tetA followed by tetB. The gene sul1 followed by sul2 were the most frequently sulfonamide resistance genes present in Salmonella. These genes are associated with plasmids, transposons, or both, and are often conjugative, highlighting the transference potential of these genes to other bacteria, environments, animals, and humans.
RESUMO
Single crystal X-ray and NMR investigations on multidomain structured N-(4,6-di-O-acetyl-2,3-dideoxy-α-D-threo-hex-2-en-2-iodo-pyranosyl)-methylsulfonamide are reported. This is the first crystallographic diffraction data report related to a 2-halo-2,3-unsaturated galactoside derivative. A complete structural study, including conformations and crystal packing, was performed by analyzing the spectroscopic data in solid state (XRD) and in solution (NMR).
Assuntos
Galactosídeos/química , Configuração de Carboidratos , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
Accurate calculation of the acid dissociation constant (pKa) has fundamental importance for the description of molecular systems with pharmacological activities. The search for a more appropriate procedure for its determination is always welcome and has aroused increasing interest from the scientific community. In this sense, this work presents a computational study involving the combination of ten DFT functionals (M062X, M06L, B3LYP, BLYP, PBEPBE, BP86, LC-BLYP, SPBE, CAM-B3LYP, LC-PBEPBE) and HF method, eight basis set functions (6-311G, 6-311 + G, 6-311G(d,p), 6-311 + G(d,p), 6-311+ +G(d,p), 6-311(2d,2p), 6-311+ +G(2d,2p), and aug-cc-pVDZ), and three solvation models (SMD, PCM, and CPCM) for an accurate sulfachloropyridazine (SCR) pKa determination. It was found that the smallest deviation (0.02 unit of pKa) between the current study and experimental result was achieved with the BLYP/6-311 + G(d,p)/PCM combination. Therefore, this combination was extended to calculate the pKa of six SCR similar molecules selected through the eletroshape similarity method. For all these molecules, the difference between the obtained results and experimental data ranged between 0.14 and 0.69 units of pKa. This feature suggests that the obtained combination can determine pKa with experimental precision for complexes that are formed by sulfonamide functional group (SO2NHR). Graphical Abstract A computational study involving the combination of different levels of theory, basis sets and solvation models for an accurate sulfanamide pKa determination.
RESUMO
Chalcones (E)-1,3-diphenyl-2-propene-1-ones, a class of biosynthetic precursor molecules of flavonoids, have a wide variety of biological applications. Besides the natural products, many synthetic derivatives and analogs became an object of continued interest in academia and industry. In this work, a synthesis and an extensive structural study were performed on a sulfonamide chalcone 1-Benzenesulfonyl-3-(4-bromobenzylidene)-2-(2-chlorophenyl)-2,3-dihydro-1H-quinolin-4-one with potential antineoplastic application. In addition, in silico experiments have shown that the sulfonamide chalcone fits well in the ligand-binding site of EGFR with seven µ-alkyl binding energy interactions on the ligand-binding site. Finally, the kinetic stability and the pharmacophoric analysis for EGFR indicated the necessary spatial characteristics for potential activity of sulfonamide chalcone as an antagonist.
Assuntos
Receptores ErbB/antagonistas & inibidores , Simulação de Acoplamento Molecular , Antineoplásicos/farmacologia , Relação Estrutura-AtividadeRESUMO
Sulfonamides have been in clinical use for many years, and the development of bioactive substances containing the sulfonamide subunit has grown steadily in view of their important biological properties such as antibacterial, antifungal, antiparasitic, antioxidant, and antitumour properties. This review addresses the medicinal chemistry aspects of sulfonamides; covering their discovery, the structure- activity relationship and the mechanism of action of the antibacterial sulfonamide class, as well as the physico-chemical and pharmacological properties associated with this class. It also provides an overview of the various biological activities inherent to sulfonamides, reporting research that emphasises the importance of this group in the planning and development of bioactive substances, with a special focus on potential antitumour properties. The synthesis of sulfonamides is considered to be simple and provides a diversity of derivatives from a wide variety of amines and sulfonyl chlorides. The sulfonamide group is a non-classical bioisostere of carboxyl groups, phenolic hydroxyl groups and amide groups. This review highlights that most of the bioactive substances have the sulfonamide group, or a related group such as sulfonylurea, in an orientation towards other functional groups. This structural characteristic was observed in molecules with distinct antibacterial activities, demonstrating a clear structure-activity relationship of sulfonamides. This short review sought to contextualise the discovery of classic antibacterial sulfonamides and their physico-chemical and pharmacological properties. The importance of the sulfonamide subunit in Medicinal Chemistry has been highlighted and emphasised, in order to promote its inclusion in the planning and synthesis of future drugs.
Assuntos
Antibacterianos/química , Antineoplásicos/química , Sulfonamidas/química , Actinobacillus/efeitos dos fármacos , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/metabolismoRESUMO
The contamination of honey, bees and hives are being an issue for discussion and critics from all communities, especially in tropical countries where due to hot climate conditions and higher tendency to food contamination the use of agrochemicals in agriculture systems are intense, as well as the use of antibiotics and food preservatives. In this work, a commercial kit for identification and quantification of sulfonamides (antibiotic class) in honey collected from local markets was used. Two samples of labeled organic honey were spiked with sulfonamide to validate the assay. Twelve commercial samples were analyzed and eleven presented residues of sulfonamides, ranging from 3.46 ug per kg of honey (result of organic sample) to 10.9 ug per kg of honey, from commercial honey. The method presented correlation of 0.92 (r); and specificity of 0.1 ug per kg of honey. The recovery tests using spiked samples with 10 and 5 ug per kg of honey , gave the recovery results of 95.5% and 82.0%, respectively. Although the contaminated samples have sulfonamides concentration lower than security limit, the honey analyzed (commercial and organic labeled samples) were no free from sulfanomides, which shows that honey has contamination problems, being anissue for all consumers, which includes children.(AU)
A contaminação do mel, abelhas e colmeias tem sido motivo de discussão critica principalmente em países tropicais, onde, devido às condições climáticas quentes e maior tendência à contaminação de alimentos, o uso de agroquímicos, antibióticos e conservantes alimentares são um problema. Neste trabalho foi utilizado um kit comercial para identificação e quantificação das sulfonamidas (antibióticos) em amostras de mel coletadas no comercio local. Duas amostras rotuladas como mel orgânico foram fortificadas com sulfonamidas para validar os imunoensaios. Das doze amostras comerciais de mel, todas apresentaram resíduos de sulfonamidas, variando de 3,46 ug por kg de mel (resultado da amostra de mel rotulado orgânico) até 10,9 ug por kg de mel, em amostra de mel comercial. O método apresentou correlação de 0,92 e especificidade de 0,1 ug por kg de mel. Os testes de recuperação de amostras fortificadas com 10 e 5 ug por kg de mel foi de 95,5 a 82,0%, respectivamente. Embora as amostras contaminadas tenham quantidades de sulfonamidas inferiores aos limites de segurança, o mel analisado (amostras comerciais e mel rotulado orgânico) contem sulfonamidas, o que mostra que o mel tem problemas de contaminação, sendo um problema de segurança alimentar para todos os consumidores, incluindo crianças.(AU)